The proposed research will examine the impact of aging on the ability of the kidney to recover 25(OH)D-1 alpha-hydroxylase activity following uninephrectomy or renal transplantation. Preliminary studies in our laboratory indicate that remnant kidneys (postuninephrectomy) in young animals exhibit a remarkable ability to compensate for decreased renal mass by means of a rapid and dramatic increase in renal 25(OH)D-1 alpha- hydroxylase activity; this compensatory response appears to be limited or absent in aged kidneys. The objective of the planned experiments is to further characterize the compensatory response of enzyme activity post-uninephrectomy and to explore the effects of age on this phenomenon. Future studies will apply the results of these experiments to studies of human donors and transplant recipients of various ages. In addition, a rat model system of renal transplantation will be developed in order to examine the effects of age of isograft, as well as recipient, on 25(OH)D-1 alpha-hydroxylase activity. The results of this research will provide important data essential for the development of therapeutic procedures in kidney donors and transplant recipients which preserve vitamin D activity and minimize subsequent bone loss.